Intra-patient dose escalation in Ewing’s sarcoma treated with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide: a retrospective review

Abstract

BackgroundData suggests that males experience less toxicity and poorer survival than females treated for Ewing’s sarcoma. We instituted an intra-patient dose escalation (DE) policy with Vincristine/Doxorubicin/Cyclophosphamide (VDC) alternating with Ifosfamide/Etoposide (IE) based on hematological nadirs and report its feasibility and safety.MethodsA retrospective review of adherence to DE guidelines and toxicities was conducted for patients who received DE with VDC/IE over 3 years at a single cancer center. Absolute neutrophil counts (ANC) was collected on days 8, 12 and 15 for cycles 1–6. DE of 10%/cycle was applied if ANC > 1.5×109/L and platelet > 100×109/L on all blood results. The primary endpoint was the proportion of patients who received appropriate DE. The secondary endpoint was to assess morbidity, changes in hematologic nadirs between gender and age and a comparison with a prior cohort of ESFT patients who did not receive DE. Gender comparisons were assessed via independent 2-sample t-tests assuming unequal variances. Within cycle changes in hematologic nadirs were assessed using repeated measures ANOVA. Relapse free survival and overall survival (OS) curves were estimated using the Kaplan-Meier method.Results23 patients were identified (mean age: 27; range 17–54). 91 decisions for DE were made (1 decision excluded because of progressive disease) with 90% concordance with guidelines. No adverse outcomes occurred as a result of the inappropriate escalation. Grade 3/4 febrile neutropenia (FN) during VDC and IE was 26.1% (6/23 patients) and 17.4% respectively with no difference for those who were DE. Males were less neutropenic after C1 and C3 of VDC compared to females (P-value C1 = 0.003; C3 = 0.005). VDC was associated with greater neutropenia on day 8 whereas IE had greater neutropenia on day 12 (P-value <0.001). During VDC, a non statistical difference in neutropenia was seen for individuals aged 15–25 (n = 13) compared with older individuals (P-value = 0.09). OS comparison for those with localized disease with a prior cohort who were not DE showed similar outcomes (P-value = 0.37).ConclusionsDE is deliverable without increased adverse outcomes. Males have less myelosuppression during VDC, and should be especially considered for DE.

Age-related Toxicity in Patients With Rhabdomyosarcoma

“…Contrary to some reports which suggest that some chemotherapy toxicities such as ototoxicity, cardiotoxicity and myelosuppression differ by gender 13, 14, 15, 2, 16 , we found no such association in the toxicities we examined. Clearly more work needs to be done in understanding the role of gender, drug metabolism and toxicity.…”

Evaluation of Adolescents’ and Young Adults’ Attitudes Toward Participation in Cancer Clinical Trials

“…In the last decade, the field of adolescent and young adult (AYA) oncology has received exponential attention, anchored on the relative poorer survival of AYA patients compared with pediatric and adult counterparts. 1 The underlying reasons for this are multifactorial, including difficulty in accessing appropriate expertise, variations in drug metabolism, 2,3 differing treatment toxicity and resultant dosing modifications, 4,5 and poor cancer clinical trial (CCT) enrollment. 6 CCTs are essential to the advancement of care because they aim to introduce novel or experimental treatment into the clinical setting.…”

Neoplastic fever in patients with bone and soft tissue sarcoma

“…Neutropenic fever is a common occurrence in patients with neutropenia after intensive chemotherapy (1)(2)(3). Neutropenic fever reportedly occurs in 37% of patients with osteosarcoma (5), 17-26% of patients with Ewing's sarcoma (6) and 8-54 of those with soft tissue sarcoma (7)(8)(9). Furthermore, patients with bone and soft tissue sarcomas are at risk of surgical site infection, which was reported to occur in 6-15% of those patients who undergo surgery (10)(11)(12).…”